ProbeSelection Probabilistic methods for identifying signatures of selection on evolutionary trees: from data to theory and back

Résumé

Selection is one of the main forces that shapes the genetic diversity observed in an evolving population, but characterizing its strength and patterns is still challenging. B-cell affinity maturation is an example of accelerated evolution under selection, which allows us to study these processes on shorter timescales than macroevolution. Here we will develop new methods to learn the properties of B cell selection from repertoire sequencing data, overcoming two issues: current methods do not allow us to go beyond neutrality (absence of selection) to infer evolutionary processes; we lack good summary statistics estimators to go beyond rejecting neutrality. We will build mathematical models of proliferating cell populations undergoing non neutral mutations, and use them to characterize patterns of selection in trees. Informed by those models we will develop inference schemes to learn the parameters of selection from the data. The outcome will be tools to characterize selection, and a basis for identifying responding lineages in clinical settings.

Mots clés

Partenaires du projet

INSB

Amaury LAMBERT

IBENS

(UMR8197) Paris, France

INP

Thierry MORA

LPENS

(UMR8023) Paris, France

B cells undergo a complex, stochastic process similar to Darwinian evolution, of recombination, mutation and selection depending on their ability to recognize the pathogen. Upon stimulation by a pathogen, B cells migrate to lymph nodes where they undergo an evolutionary process, which consists of rounds of receptor sequence diversification via enhanced DNA mutations, followed by antigen specific selection. This mutation process leads to B cell lineages of sequences descending from common ancestor sequences. The repertoire composition is therefore dynamic: new lineages are constantly being produced from an essentially infinite source by recombination, while each lineage evolves by proliferation, mutation, and selection.
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